title: Crystal structure of a human prion protein fragment reveals a motif for oligomer formation.
abstract: The structural transition of the prion protein from α-helical- to β-sheet-rich underlies its conversion into infectious and disease-associated isoforms. Here we describe the crystal structure of a fragment from human prion protein consisting of the disulfide-bond-linked portions of helices 2 and 3. Instead of forming a pair-of-sheets steric zipper structure characteristic of amyloid fibers, this fragment crystallized into a β-sheet-rich assembly of hexameric oligomers. This study reveals a never before observed structural motif for ordered protein aggregates and suggests a possible mechanism for self-propagation of misfolded conformations by such nonamyloid oligomers.
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, United States. marcinapostol@yahoo.com
authors.forename: Marcin I
authors.initials: MI
authors.lastname: Apostol
authors.forename: Kay
authors.initials: K
authors.lastname: Perry
authors.forename: Witold K
authors.initials: WK
authors.lastname: Surewicz
mesh_terms: D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D011328:Prions